Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; email:
Annu Rev Genet. 2023 Nov 27;57:461-489. doi: 10.1146/annurev-genet-071719-021856. Epub 2023 Sep 18.
Enzymes that phosphorylate, dephosphorylate, and ligate RNA 5' and 3' ends were discovered more than half a century ago and were eventually shown to repair purposeful site-specific endonucleolytic breaks in the RNA phosphodiester backbone. The pace of discovery and characterization of new candidate RNA repair activities in taxa from all phylogenetic domains greatly exceeds our understanding of the biological pathways in which they act. The key questions anent RNA break repair in vivo are () identifying the triggers, agents, and targets of RNA cleavage and () determining whether RNA repair results in restoration of the original RNA, modification of the RNA (by loss or gain at the ends), or rearrangements of the broken RNA segments (i.e., RNA recombination). This review provides a perspective on the discovery, mechanisms, and physiology of purposeful RNA break repair, highlighting exemplary repair pathways (e.g., tRNA restriction-repair and tRNA splicing) for which genetics has figured prominently in their elucidation.
半个多世纪以前，人们发现了能够磷酸化、去磷酸化和连接 RNA 5' 和 3' 末端的酶，这些酶最终被证明可以修复 RNA 磷酸二酯骨架上有意的、特定位置的内切核酸酶断裂。从所有系统发育领域的分类群中发现和鉴定新的候选 RNA 修复活性的速度大大超过了我们对它们作用的生物学途径的理解。关于体内 RNA 断裂修复的关键问题是 () 确定 RNA 切割的触发因素、试剂和靶标，以及 () 确定 RNA 修复是否导致原始 RNA 的恢复、RNA 的修饰（通过末端的丢失或获得），还是断裂 RNA 片段的重排（即 RNA 重组）。本综述提供了关于有目的的 RNA 断裂修复的发现、机制和生理学的视角，突出了具有代表性的修复途径（例如 tRNA 限制修复和 tRNA 剪接），这些途径的阐明在很大程度上依赖于遗传学。
